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Combining silver catalysis and organocatalysis: a sequential Michael addition/hydroalkoxylation one-pot approach to annulated coumarins.

Hack D, Chauhan P, Deckers K, Hermann GN, Mertens L, Raabe G, Enders D - Org. Lett. (2014)

Bottom Line: A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed.By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction.Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.

View Article: PubMed Central - PubMed

Affiliation: Institute of Organic Chemistry, RWTH Aachen University , Landoltweg 1, 52074 Aachen, Germany.

ABSTRACT
A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.

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Bioactive coumarin derivatives.
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fig1: Bioactive coumarin derivatives.

Mentions: Secondary metabolites from phytobiochemicalpathways fulfill various life-sustaining roles in plants. For example,coumarins, which originate from the shikimic acid pathway, are vitalfor the regulation of oxidative stress, hormonal regulation, and plantprotection (Figure 1).1 Interestingly, biological activity is not limited to plants only,as shown by warfarin and phenprocoumon, which belong to the classof vitamin K antagonists. Both inhibit the enzyme vitamin K epoxidereductase, thus preventing blood clotting in humans and animals.2 As a result, these anticoagulants have foundwide application as pharmaceuticals or rodenticides over the years. Although the unprotected 4-hydroxyl groupis necessary for anticoagulant activity, other biologically activenatural products have been discovered in which the oxygen is embeddedin an annulated ring structure, as found in coumestrol and frutinoneA.3,4 The former interacts with estrogen receptors ERαand -β in humans, while the latter is a potent inhibitor ofCYP1A2.


Combining silver catalysis and organocatalysis: a sequential Michael addition/hydroalkoxylation one-pot approach to annulated coumarins.

Hack D, Chauhan P, Deckers K, Hermann GN, Mertens L, Raabe G, Enders D - Org. Lett. (2014)

Bioactive coumarin derivatives.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608575&req=5

fig1: Bioactive coumarin derivatives.
Mentions: Secondary metabolites from phytobiochemicalpathways fulfill various life-sustaining roles in plants. For example,coumarins, which originate from the shikimic acid pathway, are vitalfor the regulation of oxidative stress, hormonal regulation, and plantprotection (Figure 1).1 Interestingly, biological activity is not limited to plants only,as shown by warfarin and phenprocoumon, which belong to the classof vitamin K antagonists. Both inhibit the enzyme vitamin K epoxidereductase, thus preventing blood clotting in humans and animals.2 As a result, these anticoagulants have foundwide application as pharmaceuticals or rodenticides over the years. Although the unprotected 4-hydroxyl groupis necessary for anticoagulant activity, other biologically activenatural products have been discovered in which the oxygen is embeddedin an annulated ring structure, as found in coumestrol and frutinoneA.3,4 The former interacts with estrogen receptors ERαand -β in humans, while the latter is a potent inhibitor ofCYP1A2.

Bottom Line: A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed.By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction.Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.

View Article: PubMed Central - PubMed

Affiliation: Institute of Organic Chemistry, RWTH Aachen University , Landoltweg 1, 52074 Aachen, Germany.

ABSTRACT
A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.

Show MeSH